SAN FRANCISCO, Mar 08, 2001 (United Press International via COMTEX) -- Scientists at the University of California, San Francisco have worked out the biochemical process through which common bacteria become resistant to the antibiotics used to combat them.

As they will report Friday in the journal Science, interactions between proteins on the surface of staphylococci bacteria and surrounding antibiotics turn on bacterial genes that neutralize the medication.

The bacteria cause staph infections, which are responsible for conditions "as relatively benign as boils and as serious as infections of the heart valves, deep bone infections, or toxic shock syndrome," said Dr. Henry Chambers, a study author and UCSF professor of medicine.

The surface proteins are specialized molecules that penetrate through the cell membrane. Chambers and colleagues have dubbed them sensor proteins. They say the sensor-antibiotic interaction triggers a unique and complex biochemical pathway that turns on genes that, in turn, direct the production of enzymes that neutralize the antibiotic, allowing the bacteria to survive.

No one has described this sequence of events before, commented Dr. Joseph Bosilevac, a researcher in microbiology and immunology at Virginia Commonwealth University, Richmond.

Bosilevac, who was not involved in the research, told United Press International the new information might be used to develop drugs that interfere with the process and prevent the development of resistance.

The staph enzymes are called beta-lactamases, and normally the genes that code for their expression are turned off, or repressed, said Chambers.

However, when the cell senses the presence of a class of antibiotics known as beta-lactams, that repression is lifted, allowing it to manufacture enzymes that destroy the drugs. Examples of beta-lactam antibiotics include penicillin, ampicillin, and amoxicillin.

According to the researchers, the encounter between an antibiotic and a sensor protein causes that protein to split into two fragments. One of those fragments then functions as an enzyme that helps reverse the repression of the gene that codes for the enzymes that break down the antibiotics. The result: bacterial resistance.

"The surprising feature is that the sensor protein is actually a fusion of two proteins," Chambers told UPI. "On the outside of the cell is the detector end that binds penicillin. On the inside is the business end, which removes the repressor."

As for developing new antibiotics, bacteria sometimes devise alternative survival strategies that bypass the metabolic pathways targeted by many drugs, Chambers said. To be effective, the drug would have to attack "a pathway that can't be easily circumvented or aborted."

However, it might be possible to get around that problem by using several drugs, or drugs that attack the bacteria at more than one site. Still, both Chambers and Bosilevac agree it will take years before any drugs that might arise as a result of these findings appear on the market.

"The interesting part to me is that this is such a novel signaling mechanism: a self-acting (enzyme) that inactivates a repressor has not been described before," said Chambers. The discovery could open up new avenues of research to investigators who had not considered such a possibility before, he added.

(Reported by Norra MacReady in Los Angeles.)

Copyright 2001 by United Press International.

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